Process for the synthesis of fluoroorganic compounds

ABSTRACT

The present invention relates to a fluorination method for the synthesis of halofluoroorganic compounds which can be used, inter alia, as precursors in the synthesis of 2,3-unsaturated fluoroorganic carbonyl compounds comprising a fluorine substituent in the 2 position.

The present invention relates to a fluorination method for the synthesisof halofluoroorganic compounds which can be used, inter alia, asprecursors in the synthesis of fluoroorganic compounds. It also relatesto certain halofluoroorganic compounds, to a process for the synthesisof fluoroorganic compounds and to the use of the said fluoroorganiccompounds as a synthetic intermediate, in particular as a (co)monomer.

2,3-Unsaturated organic carbonyl compounds comprising a fluorinesubstituent in the 2 position, such as, for example, 2-fluoropropenoicacid derivatives, can be used as an intermediate in the synthesis oforganic compounds, particularly in the manufacture of fluorooligomers orfluoropolymers which can be used, for example, in the manufacture ofsynthetic glass of high mechanical strength or in the manufacture ofoptical fibres.

A review article (Boguslavskaja et al., Russian Chemical Reviews, 59(9), 1990, p. 906-917) describes methods for the synthesis of2-fluoropropenoic acid derivatives. The various methods described inthis article however exhibit numerous disadvantages, such as, interalia, an unsatisfactory overall yield of 2-fluoropropenoic acidderivatives, a high number of stages, difficult accessibility to theprecursors of the 2-fluoropropenoic acid derivatives or alternativelyuse of reactants which are difficult to access and expensive, such asinterhalogen compounds.

The invention is targeted at providing an efficient process for thesynthesis of 2,3-unsaturated organic carbonyl compounds comprising afluorine substituent in the 2 position and in particular of2-fluoro-2-alkenoic acid derivatives which does not exhibit theabovementioned disadvantages. The invention is also targeted atproviding efficient precursors of organic carbonyl compounds, the saidprecursors being able to be obtained economically from readilyaccessible products.

The invention consequently relates to a fluorination method for thesynthesis of a halofluoroorganic compound of general formulaHR′R″C—CXF—(C═O)—Y (I) in which X denotes a halogen atom and Y, R′ andR″ denote substituents, according to which fluorination method hydrogenfluoride is reacted with an organic compound which corresponds to ageneral formula chosen from R′R″C═CX—(C═O)—Y (II) andR′R″HC—CX1X2—(C═O)—Y (III) in which X1 and X2 denote halogen atoms.

It has been found that the halofluoroorganic compounds of generalformula (I) in which X denotes a halogen atom are efficient precursorsof 23-unsaturated organic carbonyl compounds comprising a fluorinesubstituent in the 2 position. The fluorination method according to theinvention makes possible access to the said halofluoroorganic compoundswith a high yield and a high selectivity from economical and readilyaccessible starting materials and reactants.

For the purposes of the present invention, the term ‘halogen atom’ andthe term ‘halo’ are intended to denote in particular chlorine, bromineand iodine. Chlorine and bromine are preferred among these halogens.Chlorine is very particularly preferred.

For the purposes of the present invention, Y denotes a substituent. Itis clearly understood that, between two compounds with different generalformulae, Y is not necessarily identical, as it is optionally possiblefor Y to undergo a modification during a chemical reaction in thecontext of the invention. Y can be chosen, for example, from H, alkyl,haloalkyl, aryl, OH, OR, NH₂, NHR, NR₂ and SR in which R denotes asubstituent other than hydrogen which, may be selected, for example fromthe group consisting of alkyl, alkenyl and aryl groups. The organiccompound comprising Y is then chosen from aldehydes, ketones, carboxylicacids, esters, amides and thioesters. In the context of the invention,the organic compound comprising Y is often chosen from carboxylic acids,esters, amides and thioesters. It is preferably chosen from carboxylicacids and esters.

For the purposes of the present invention, R′ and R″ are intended todenote substituents in the various compounds. R′ and R″ can be identicalor different. In an alternative form, the R′ and R″ substituents arechosen from hydrogen and fluorine, chlorine, bromine and iodine atoms.These substituents are preferably chosen from hydrogen, fluorine andchlorine. In another alternative form, the R′ and R″ substituents arechosen from hydrogen and hydrocarbonaceous substituents, such as, forexample, alkyl, alkenyl or aryl groups. Compounds in which R′ and R″denote hydrogen atoms are preferred for the purposes of the presentinvention.

In a first preferred alternative form of the fluorination methodaccording to the invention, the organic compound is a carboxylic acidwhich can additionally carry substituents as described above.Particularly preferred examples of such acids are 2,2-dihalopropionicacids and 2-halopropenoic acids.

2,2-Dichloropropionic acid is highly suitable as 2,2-dihalopropionicacid. This is because 2,2-dichloropropionic acid has been marketed as aherbicide. It is consequently readily accessible in industrial amountsand easy synthetic methods are available, such as, for example, thechlorination of propionic acid disclosed, inter alia, in JP-A-45/039804.

2-Chloropropenoic acid is highly suitable as 2-halopropenoic acid. Itcan be easily obtained, for example from acrylic acid according to themethods disclosed in BE 786 464 and BE 817 678.

In a second preferred alternative form, the fluorination methodaccording to the invention applies to the production of esters of2-halo-2-fluorocarboxylic acids by reaction of hydrogen fluoride withesters of carboxylic acids as mentioned above.

In this case, the carboxyl group of the carboxylic acid is generallyesterified with a radical comprising at least 1, more frequently atleast 2, carbon atoms. The carboxyl group of the carboxylic acid isgenerally esterified with a radical comprising at most 20, morefrequently at most 12, carbon atoms. The radical often comprises atleast one substituent chosen from chlorine and fluorine. In analternative form, the radical is an alkyl chain comprising at least onetrichloromethyl group. In this alternative form, the radical ispreferably a 2,2,2-trichloroethyl radical. In another alternative form,the radical is an alkyl chain comprising at least one trifluoromethylgroup. In this alternative form, the radical is preferably chosen fromthe 2,2,2-trifluoroethyl radical and the 1,1,1,3,3,3-hexafluoro-2-propylradical. The esters can be obtained by conventional methods, for exampleby reaction of the carboxylic acid or of an acid halide derived fromthis carboxylic acid with the alcohol corresponding to the desiredradical.

It is clearly understood that the esters of 2-halo-2-fluorocarboxylicacids can also be obtained by subsequent esterification of2-halo-2-fluorocarboxylic acids obtained according to the fluorinationmethod according to the invention.

In the fluorination method according to the invention, the reactionbetween the organic compound and the hydrogen fluoride can be carriedout in the presence of a fluorination catalyst.

Mention may be made, among the catalysts which can be used, ofderivatives of the metals chosen from the metals from Groups IIIa, IVaand b, Va and b, VIb of the Periodic Table of the Elements (IUPAC 1970)and their mixtures. Titanium, tantalum, molybdenum, boron, tin andantimony derivatives are more especially selected. Preferably, titaniumor tin derivatives are employed. Tin derivatives are particularly wellsuited. Mention may be made, as derivatives of the metals, of salts andmore particularly halides. The choice is preferably made from chlorides,fluorides and chlorofluorides. Catalysts which are particularlypreferred in the fluorination method according to the invention aretitanium and tin chlorides, fluorides and chlorofluorides and theirmixtures.

Titanium tetrachloride and tin tetrachloride are particularly wellsuited. Tin tetrachloride is preferred.

The reaction can also be carried out in the absence of catalyst. Thisalternative form is particularly well suited when an organic compound ofgeneral formula (II) described above is reacted with hydrogen fluoride.

The reaction is preferably carried out in the liquid phase.

The reaction can be carried out continuously or batchwise. A batchwisereaction is well suited.

The reaction can be carried out in the absence of solvent. It is alsopossible to use a solvent in which the organic compound is soluble. Suchsolvents are, for example, polar solvents, such as nitrites, amides andesters.

In the reaction, the hydrogen fluoride and the organic compound aregenerally employed in an HF/organic compound molar ratio of at least 1.The molar ratio is preferably at least 3. The HF/organic compound molarratio is generally at most 20. The molar ratio is preferably at most 12.

If a catalyst is used in the reaction, the catalyst and the organiccompound are generally employed in a catalyst/organic compound molarratio of at least 0.01. This molar ratio is preferably at least 0.05.The catalyst/organic compound molar ratio is generally at most 1. Thismolar ratio is preferably at most 0.5.

The temperature of the reaction is generally at least 50° C. Thetemperature is more frequently at least 80° C. The temperature ispreferably at least 90° C. The temperature of the reaction is generallyat most 200° C. The temperature is more frequently at most 150° C. Thetemperature is preferably at most 130° C.

The pressure of the reaction is generally at least 1 bar. The pressureis generally at most 100 bar, preferably at most 50 bar.

In a particular embodiment, it might be advantageous to limit theconversion of the organic compound in order to optimise the yield ofhalofluoroorganic compound. In this embodiment, the conversion of theorganic compound is generally kept at 80% or less, preferably about 70%or less.

The halofluoroorganic compound can be recovered from the reaction mediumby separation techniques known as such, such as, for example, inparticular a distillation. Unconverted organic compound may be suitablyrecycled to the reaction with hydrogen fluoride.

The halofluoroorganic compounds resulting from the fluorination reactioncan be subjected to subsequent reactions intended to modify the Ysubstituent, such as, for example, the esterification reaction,mentioned above, of a carboxylic acid.

When Y is OH, the halofluoroorganic compound is a2-halo-2-fluorocarboxylic acid. The 2-halo-2-fluorocarboxylic acid ispreferably a 2-halo-2-fluoropropionic acid. 2-Chloro-2-fluoropropionicacid is more particularly preferred.

When Y is OR, the halofluoroorganic compound is an ester of2-halo-2-fluorocarboxylic acid. The preferred esters are the esters ofthe preferred 2-halo-2-fluorocarboxylic acids in which the carboxylgroup of the carboxylic acid is esterified with a radical comprising atleast one atom chosen from chlorine and fluorine and more particularlythe radicals mentioned above.

The invention also relates to an organic product composed essentially ofhalofluoroorganic compounds as described above. The invention alsorelates in particular to 2-halo-2-fluorocarboxylic acids and esters of2-halo-2-fluorocarboxylic acids. The invention also relates to2-chloro-2-fluoropropionic acid.

The halofluoroorganic compounds which can be obtained according to thefluorination method according to the invention are intermediates whichcan be used in organic synthesis. They are well suited to the synthesisof fluoroorganic compounds of general formula R′R″C═CF—(C═O)—Y (IV).They are particularly well suited to the synthesis of2-fluoro-2-alkenoic acids and esters of 2-fluoro-2-alkenoic acids.

The invention consequently also relates to a process for the synthesisof a fluoroorganic compound of general formula R′R″C═CF—(C═O)—Y (IV)comprising a stage (a) in which a precursor comprising ahalofluoroorganic compound of general formula HR′R″C—CXF—(C═O)—Y (I), inwhich X denotes a halogen atom, is subjected to a dehydrohalogenationreaction.

In the process according to the invention, the precursor is oftencomposed essentially of a halofluoroorganic compound of general formulaHR′R″C—CXF-(C═O)—Y (I) as described above. The precursor is preferablychosen from 2-halo-2-fluorocarboxylic acids and esters of2-halo-2-fluorocarboxylic acids. In the process according to theinvention, the precursor was preferably obtained according to thefluorination method according to the invention. The fluoro-organiccompounds resulting from the dehydrohalogenation reaction can besubjected to subsequent reactions intended to modify the Y substituent,such as, for example, the esterification reaction, mentioned above, of acarboxylic acid.

In a particular embodiment, the precursor comprises, in addition to thea halofluoroorganic compound of general formula (I), at least an organiccompound selected from the organic compounds of general formulae (II)and (III) described above. Such a precursor may be obtained, forexample, by a simple separation of organic constituants from inorganicconstituants of the reaction medium obtained by the fluorination methodof the invention, for example by extraction or distillation. Organiccompound of general formula (III) is generally converted by thedehydrohalogenation reaction into an organic compound of general formula(II). The organic compounds of general formula (II) or (III) which, inthis particular embodiment, are contained in the reaction mixtureproduced by the dehydrohalogenation reaction, may be suitably separatedfrom the fluoroorganic compound of general formula (IV) by separationtechniques such as, for example, a distillation or crystallisation. Theorganic compounds of general formula (II) or (III) can be preferablyrecycled to a reaction with hydrogen fluoride according to thefluorination method of the invention.

The dehydrohalogenation reaction can be carried out, for example, byreaction with a base, by the thermal route or by reaction in thepresence of a dehydrohalogenation catalyst, such as, for example, anorganometallic catalyst.

The reaction with a base is preferred. Mention may be made, as bases, ofalkali metal hydroxide solutions, amines and alkoxides. Mention may inparticular be made of aqueous sodium hydroxide solutions.

The dehydrohalogenation temperature is generally at least 40° C. Thetemperature is preferably at least 60° C. The dehydrohalogenationtemperature is generally at most 200° C. The temperature is preferablyat most 150° C.

The concentration of the precursor in the reaction medium is generallyat least 5% by weight. The concentration is generally at most 50% byweight.

The pressure at which the dehydrohalogenation is carried out isgenerally from 1 bar to 20 bar.

The fluoroorganic compound can be recovered by conventional techniques,such as, for example, an extraction. Nitriles, such as, in particular,propionitrile, or ethers, such as, in particular, diethyl ether, arewell suited as extraction solvent.

In a preferred alternative form, the process according to the inventioncomprises

-   (a) a stage in which an organic compound which corresponds to a    general formula chosen from R′R″C═CX—(C═O)—Y (II) and    R′R″HC—CX1X2-(C═O)—Y (III) as described above is reacted according    to the fluorination method according to the invention to produce a    halofluoroorganic compound of general formula HR′R″C—CXF—(C═O)—Y    (I);-   (b) a stage in which the halofluoroorganic compound is subjected to    a dehydrohalogenation;-   (c) a stage in which optionally at least one reaction intended to    modify the Y substituent is carried out;-   (d) a stage in which a fluoroorganic compound of general formula    R′R″C═CF—(C═O)—Y (IV) is recovered.

The process according to the invention is particularly well suited tothe production of fluoroorganic compounds chosen from 2-fluoropropenoicacid and esters of 2-fluoropropenoic acid.

The invention also relates to the use of the fluoroorganic compound ofgeneral formula R′R″C═CF—(C═O)—Y (IV) obtained according to the processaccording to the invention as monomer or comonomer in a process for themanufacture of a fluoropolymer or fluorooligomer.

The term ‘fluorooligomer’ is understood to denote an organic bodycomprising at least 2 and at most 50 monomer units, including at leastone monomer unit obtained according to the process according to theinvention. The term ‘fluoropolymer’ is understood to denote an organicbody comprising more than 50 monomer units, including at least onemonomer unit obtained according to the process according to theinvention.

The polymerization reaction can, for example, be a radicalpolymerization. The molecular mass can be controlled by conventionalmethods.

The examples given below are intended to illustrate the inventionwithout, however, limiting it.

EXAMPLE 1 Synthesis of 2-chloro-2-fluoropropionic Acid

100 g of 2,2-dichloropropionic acid, 123 g of HF and 33 g of SnCl₄ wereintroduced into a 0.5 l stainless steel autoclave. The reaction mixturewas heated at 110° C. for 18 h. The liquid phase collected after coolingthe autoclave and degassing was analysed by GC (gas chromatography). Theconversion of the 2,2-dichloropropionic acid was 75%. The selectivityfor 2-chloro-2-fluoropropionic Acid was 97%.

EXAMPLE 2 Synthesis of 2-chloro-2-fluoropropionic Acid

45 g of 2,2-dichloropropionic acid, 61 g of HF and 17.5 g of SnCl₄ wereintroduced into a 0.5 l stainless steel autoclave. The reaction mixturewas heated at 120° C. for 5 h. The liquid phase collected after coolingthe autoclave and degassing was analysed by GC. The conversion of2,2-dichloropropionic acid was 61%. The selectivity for2-chloro-2-fluoropropionic acid was 70%.

EXAMPLE 3 Synthesis of 2,2,2-trifluoroethyl 2-chloro-2-fluoropropionate

Stage A—Synthesis of 2,2,2-trifluoroethyl 2,2-dichloropropionate: 20 gof 2,2-dichloropropionic acid and 18 g of thionyl chloride were heatedat reflux for 5 h. After cooling, the liquid phase was analysed by GC.The degree of conversion of the 2,2-dichloropropionic acid was 78%. 10 gof 2,2-dichloropropionyl chloride obtained and 6 g of2,2,2-trifluoroethanol were introduced into a round-bottomed flaskplaced in an ice bath. 6.5 g of triethylamine were added to the reactionmixture over 2 h. After reacting for an additional 2 h, approximately 50ml of water were added. The aqueous and organic phases were subsequentlyseparated and the organic phase was analysed by GC. The2,2,2-trifluoroethanol was converted to 77%. The yield of ester, basedon the amount of 2,2-dichloropropionic acid employed in the first stage,was 65%.

Stage B—Hydrofluorination of 2,2,2-trifluoroethyl 2,2-dichloropropionate: 28 g of 2,2,2-trifluoroethyl 2,2-dichloropropionate, 30 g of HF and2.7 g of SnCl₄ were introduced into a 0.5 l stainless steel autoclave.The reaction mixture was heated at 100° C. for 24 h. The liquid phasecollected after cooling the autoclave and degassing was analysed by GC.The conversion of the ester was 84%. The selectivity for2,2,2-trifluoroethyl 2-chloro-2-fluoropropionate was 95%.

EXAMPLE 4 Synthesis of 2-fluoroacrylic Acid

31 g of 2-chloro-2-fluoropropionic acid were dissolved in 320 ml of a 2NNaOH solution and heated at 100° C. for 24 h. The medium wassubsequently acidified with 140 ml of 2N HCl. The 2-fluoroacrylic acidwas extracted with two times 200 ml of diethyl ether. 20 g of2-fluoroacrylic acid were recovered after evaporation of the ether. Theyield of 2-fluoroacrylic acid, based on the amount of2-chloro-2-fluoropropionic acid employed, was 90%.

EXAMPLE 5 Synthesis of 2,2,2-trifluoroethyl 2-fluoroacrylate

10 g of 2-fluoroacrylic acid and 16 g of thionyl chloride were heated atreflux for 6 h. After cooling, the liquid phase was analysed by GC. Theconversion of the 2-fluoroacrylic acid was complete. 10 g of2-fluoroacryloyl chloride obtained and 13 g of 2,2,2-trifluoroethanolwere introduced into a round-bottomed flask placed in an ice bath. 13 gof triethylamine were added portionwise to the reaction mixture. Afterreacting for an additional 3 h, approximately 30 ml of water were added.The aqueous and organic phases were subsequently separated and theorganic phase was analysed by GC. The conversion of the2,2,2-trifluoroethanol was 77%. The yield of ester, based on the amountof 2-fluoroacrylic acid employed in the first stage, was 70%.

EXAMPLE 6 Synthesis of 1,1,1,3,3,3,-hexafluoro-2-propyl 2-fluoroacrylate

12 g of 2-fluoroacryloyl chloride and 27 g of1,1,1,3,3,3-hexafluoro-2-propanol were introduced into a round-bottomedflask placed in an ice bath. 16 g of triethylamine were addedportionwise to the reaction mixture. After reacting for an additional 3h, approximately 70 ml of water were added. The aqueous and organicphases were subsequently separated and the organic phase was analysed byGC. The conversion of the 1,1,1,3,3,3-hexafluoroisopropanol was 68%. Theyield of ester, based on the amount of 2-fluoroacrylic acid employed inthe first stage, was 66%.

EXAMPLE 7 Synthesis of 2,2,2-trichloroethyl 2-fluoroacrylate

12 g of 2-fluoroacryloyl chloride and 26 g of 2,2,2-trichloroethanolwere introduced into a round-bottomed flask placed in an ice bath. 17 gof triethylamine were added portionwise to the reaction mixture. Afterreacting for an additional 3 h, approximately 50 ml of water were added.The aqueous and organic phases were subsequently separated and theorganic phase was analysed by GC. The conversion of the2,2,2-trichloroethanol was 52%. The yield of ester, based on the amountof 2-fluoroacrylic acid employed in the first stage, was 67%.

It is apparent that the fluorination method according to the inventionmakes possible efficient synthesis of halofluoroorganic syntheticintermediates which are advantageous in particular as precursors of2,3-unsaturated carbonyl compounds carrying a fluorine substituent inthe 2 position. The process according to the invention makes possibleefficient access in a way which can be operated industrially to thesefluoroorganic compounds, which can be used in particular as monomer orcomonomer in the manufacture of fluoropolymers or fluorooligomers.

1. A process for the synthesis of a fluoroorganic compound of generalformula (IV),R′R″C═CF—(C═O)—Y (IV), comprising a stage (a) in which ahalofluoroorganic compound of general formula (I),HR′R″C—CXF—(C═O)—Y (I), in which X denotes a halogen atom and Y is H,alkyl, haloalkyl, aryl, OH, OR, NH₂, NHR, NR₂ or SR in which R is alkyl,alkenyl or aryl, R′ is hydrogen, fluorine, chlorine, iodine orhydrocarbonaceous substituents, R″ is hydrogen, fluorine, chlorine,iodine or hydrocarbonaceous substituents, is subjected to adehydrohalogenation reaction.
 2. A process for the synthesis of afluoroorganic compound of general formula (IV),R′R″C═CF—(C═O)—Y (IV), comprising a stage (a) in which a precursorconsists essentially of a halofluoroorganic compound of the generalformula (I),HR′R″C—CXF—(C═O)—Y (I), in which X denotes a halogen atom and Y is H,alkyl, haloalkyl, aryl, OH, OR, NH₂, NHR, NR₂ or SR in which R is alkyl,alkenyl or aryl, R′ is hydrogen, fluorine, chlorine, iodine orhydrocarbonaceous substituents, R″ is hydrogen, fluorine, chlorine,iodine or hydrocarbonaceous substituents, is subjected to adehydrohalogenation reaction.
 3. The process according to claim 1, inwhich the halofluoroorganic compound is selected from the groupconsisting of 2-halo-2-fluorocarboxylic acids and esters of2-halo-2-fluorocarboxylic acids.
 4. The process according to claim 1, inwhich the halofluoroorganic compound was obtained according to asynthesis wherein hydrogen fluoride is reacted with an organic compoundwhich corresponds to a general formula (II) or (III),R′R″C═CX—(C═O)—Y (II)R′R″HC—CX1X2-(C═O)—Y (III), in which X1 and X2 denote halogen atoms, Xdenotes a halogen atom and Y is H, alkyl, haloalkyl, aryl, OH, OR, NH₂,NHR, NR₂ or SR in which R is alkyl, alkenyl or aryl, R′ is hydrogen,fluorine, chlorine, bromine, iodine or hydrocarbonaceous substituents,and R″ is hydrogen, fluorine, chlorine, bromine, iodine orhydrocarbonaceous substituents.
 5. The process as claimed in claim 1,wherein R′ and R″ are hydrogen.
 6. A process for the manufacture of afluoropolymer or fluorooligomer comprising polymerizing or oligomerizingthe monomer of the fluoroorganic compound of general formula (IV)R′R″C═CF—(C═O)—Y (IV), obtained according to the process according toclaim
 1. 7. The process as claimed in claim 5, wherein said organiccompound comprising Y is OH or OR selected from the group consisting ofcarboxylic acids and esters.
 8. A process for the synthesis of afluoroorganic compound of general formula (IV),R′R″C═CF—(C═O)—Y (IV), comprising a stage (a) in which ahalofluoroorganic compound of general formula (I),HR′R″C—CXF—(C═O)—Y (I), in which X denotes a halogen atom and Y is H,alkyl, haloalkyl, aryl, OH, OR, NH₂, NHR, NR₂ or SR in which R is alkyl,alkenyl or aryl, R′ is hydrogen, fluorine, chlorine, iodine orhydrocarbonaceous substituents, R″ is fluorine, chlorine, iodine orhydrocarbonaceous substituents, is subjected to a dehydrohalogenationreaction.